Do sodium channel blockers have neuroprotective effect after onset of ischemic insult?

OBJECTIVE: Cerebral ischemia causes a series of pathophysiologic events that may result in cerebral infarct. Some neurons are more vulnerable to ischemia, particularly pyramidal neurons in the hippocampal CA1 region. Pharmacologic intervention for treatment of cerebral ischemia aims to counteract secondary neurotoxic events or to interrupt the progression of this process. In the present study, we compare the neuroprotective effects of sodium channel blockers (mexiletine, riluzole and phenytoin) and investigate whether they have neuroprotective effect when given after ischemic insult. METHODS: A transient global cerebral ischemia model was performed in this study by clipping bilateral common carotid arteries during 45 minutes. Riluzole (8 mg/kg), mexiletine (80 mg/kg) and phenytoin (200 mg/kg) were injected into the rats intraperitoneally 30 minutes before or after reperfusion. Lipid peroxidation levels and cerebral water contents were evaluated 24 hours after ischemia. Histopathologic assessment of hippocampal region was determined 7 days after ischemia. RESULTS: Riluzole, mexiletine and phenytoin treatment after global ischemia significantly decreased water content of the ischemic brain (p<0.05 for each). No significant difference was observed in cerebral edema among the drug treatment groups (p>0.05). When pre-treatment and post-treatment groups were compared with each other, only riluzole pre-treatment group revealed better result for cerebral edema (p<0.05). Pre-treatment with these drugs revealed significantly better results for the malonyldialdehyde (MDA) level and the number of survival neuron on the hippocampal region than the post-treatment groups. CONCLUSION: It is demonstrated that riluzole, mexiletine and phenytoin are potent neuroprotective agents in the rat model of transient global cerebral ischemia, but they are more effective when given before onset of the ischemia.     

Effect of prenatal exposure to an anti-inflammatory drug on neuron number in cornu ammonis and dentate gyrus of the rat hippocampus: a stereological study

Prenatal exposed to an anti-inflammatory drug is a major problem for the developing central nervous system. It is not well known the effect of prenatal exposed to a non-steroidal anti-inflammatory drug on the hippocampus. Total neuron number in one side of the cornu ammonis (CA) and gyrus dentatus (GD) of the hippocampal formation in control and drug-treated (diclofenac sodium, DS) groups of male rats was estimated using the optical fractionator technique. Each main group has also two subgroups that are 4 weeks old (4W-old) and 20 weeks old (20W-old). In CA, no significant difference between 4W-old DS-treated and their control was found, but a significant difference was observed between 20W-old DS-treated and their controls. A decreasing of neuron number was 12% for 20W-old DS-treated group. In GD, a decreasing of the granule cell number in 4W-old of DS-treated group was seen but an increasing of granule cell number was found in the 20W-old drug-treated rats in comparison to its control group, 7% and 9%, respectively. Although an increasing of neuron number in CA at the control group was seen with age, from 4th week to 20th week (10%), age-dependent substantial granule cell decline (17%) was observed in GD. No age effect on the total cell numbers of CA and GD of the drug-treated groups was seen in comparison to 4W-old week and 20W-old. A pronounced neuron loss observed in the drug-treated group may be attributed to the neurotoxicity of diclofenac sodium (DS) on the developing hippocampal formation. Age-dependent neuron increase in the CA of 20W-old and neuron decline in GD of 20W-old control groups may be a result of a dual effect of saline injection during the fetal life, since these animals were exposed to a stress of 15-day-period of saline injection, prenatal stress. The reason of no age effect on CA and GD cell number in the drug-treated groups may be attributed to the depletion of the progenitor cells due to neurotoxicity of DS in the fetal life of these animals.     

Effect of chronic treatment of haloperidol on the rat liver: a stereological and histopathological study

Haloperidol is commonly used in therapy for patients with acute and chronic schizophrenia. Because it can have some adverse effects on specific target organs such as the liver, we analyzed whether haloperidol exerts a toxic effect on rat liver by means of stereological and histopathological methods. Fifteen adult male rats, divided into three groups, were used in the experiments. Once a day for 6 weeks, either saline or 0.4 or 0.8 mg kg⁻¹ doses of haloperidol were given interperitoneally to the control, low-dose, and high-dose groups, respectively. At the end of the experiment, rats were killed by an overdose of a general anesthetic, and the livers were dissected out, fixed for sectioning, and evaluated using stereological and histopathological methods. Hepatocyte numbers were found to be 271.672, 291.072, and 238.415 hepatocytes per cubic millimeter in the liver of the control, low-dose, and high-dose groups, respectively. The differences between high-dose and control groups and also between high-dose and low-dose groups were significant (p < 0.05). Our histopathological findings at both the structural and the ultra-structural level were confirmed by stereological estimations. Results suggest a relationship between haloperidol dose and toxic effects on the liver, and they indicate that a high dose of haloperidol may result in irreversible liver damage. This research was conducted in the Laboratory of Pharmacology at Ataturk University, School of Medicine, 25240 Erzurum/Turkey and the Laboratory of Histology and Embryology, School of Medicine, at Ataturk University, 25240 Erzurum/Turkey. None of the authors has a commercial interest, financial interest, and/or other relationship with manufacturers of pharmaceuticals, laboratory supplies, and/or medical devices or with commercial providers of medically related services.     

A New Technique of Biliary Reconstruction After “High Hilar Resection” of Hilar Cholangiocarcinoma with Tumor Extension to Secondary and Tertiary Biliary Radicals

Background  Radical operation for hilar cholangiocellular carcinoma, including extended hepatic resection, seems to improve prognosis by increasing the surgical curability rate. Nevertheless, high postoperative morbidity and mortality have been reported in patients with obstructive jaundice. We describe the technique of “high hilar resection” and a modification of bilioenteric anastomosis for drainage of the multiple secondary or tertiary biliary radicals. Methods  Ten patients with advanced hilar cholangiocellular carcinoma underwent a high hilar resection with complete parenchymal preservation, and the biliary drainage was reconstructed by a sheath-to-enteric hepaticojejunostomy. Because of the technical difficulty caused by anastomosis line in the range of the biliary sheath, a modification was performed by dividing the biliary apertures of segments 5 and 4b. Results  A high hilar resection was successfully performed, and all patients were discharged from the hospital in good condition. No patient died postoperatively. The proximal resection margin was tumor-free in all patients. One patient died after 29 months of peritoneal carcinomatosis. None of the patients developed local recurrence around the hepaticojejunostomy. The remaining nine patients are alive after a mean follow-up of 28.8 months after surgery without any signs of recurrence. Conclusion  In highly selected patients with advanced hilar cholangiocellular carcinoma, a high hilar resection is technically safe and oncologically justifiable. In combination with our new technique of sheath-to-enteric anastomosis, the patients considerably benefit from the preservation of liver parenchyma with low postoperative morbidity and very short in-hospital stay.     

Serum tumor marker CA19-9 in the follow-up of patients with cystic echinococcosis

BACKGROUND: The aim of this study was to compare results of the determination of carcinoembryonic antigen, carbohydrate antigens, alpha-fetoprotein, and human chorionic gonadotropin before and after surgical and pharmacologic treatment in patients with cystic echinococcosis (CE). METHODS: Serum samples were obtained from 40 CE patients (all with cysts in the liver) and from 10 sex- and age-matched healthy donors (control group). Serum samples were drawn (1) before (presurgical group) and after (postsurgical group, including a 3-month cycle of albendazole) surgical and pharmacologic treatment. Serum tumor markers were measured, and indirect hemagglutination assay was performed. RESULTS: In 90% of confirmed cases of CE, indirect hemagglutination assay was positive. Mean (SD) serum CA19-9 concentrations for all patients in the presurgical and postsurgical groups were 45.1 +/- 30 kU/L and 17.02 +/- 11 kU/L, respectively. CA19-9 concentrations were significantly greater in CE patients in the presurgical compared with the control group. Also, increased CA19-9 concentrations decreased significantly in the postsurgical compared with the presurgical group. CONCLUSIONS: A significant decrease in serum CA19-9 concentrations after surgical and pharmacologic therapy was demonstrated in the clinical follow-up of patients with CE (patients were tested 3 months after surgery). If our findings are confirmed and more-sensitive methods are developed for measuring serum CA19-9 concentrations, new and interesting perspectives will be gained for the monitoring and treatment of patients with CE.     

Metachronous non-Hodgkin's lymphoma in a patient with localized prostate cancer

Introduction A higher frequency of second malignancies is observed in patients with prostate cancer. We report a case of indolent non-Hodgkin's lymphoma diagnosed 2 years after prostate carcinoma. Case report A 65-year-old man with diagnosis of localized prostate adenocarcinoma was presented with fatigue 2 years after prostatectomy operation. Abdominal ultrasonography showed hepatomegaly and paraaortocaval, parailiac, and perivascular multiple lymph nodes. The complete blood count revealed anemia and thrombocytopenia. Bone marrow biopsy demonstrated small lymphocytic lymphoma. Conclusion Lymphoma should be suspected in cases with newly appeared adenopathy and/or cytopenias during follow-up. In patients with clinically organ-confined prostate cancer, indolent lymphoma should be in the differential diagnosis of newly appeared lymphadenopathy.